(a) Technical Field
The present invention relates to a temperature-sensitive polyethylene glycol/polyester block copolymer having a bioactive functional group introduced into a side chain thereof, more particularly to a temperature-sensitive polyethylene glycol/polyester block copolymer including a lactide segment having a specific bioactive functional group such as a benzyl ether group introduced into a side chain thereof.
(b) Background Art
At present, research has been focused on temperature-sensitive hydrogels for application to drug delivery systems and tissue engineering applications utilizing their change in physical and chemical properties in response to external stimulation. For a temperature-sensitive hydrogel to be utilized for injectable drug delivery systems and tissue engineering applications, it should exhibit low viscosity, fast gelation, biodegradability and low molecular weight to be easily cleared from human body. Further, to be used as a biomaterial, it should be biocompatible and should not damage cells or organs during degradation or clearance from human body.
To solve this problem, block copolymers of a biodegradable and temperature-sensitive polyethylene glycol with a biodegradable ester such as caprolactone, lactide, p-dioxanone and trimethylene carbonate, which exhibit different sol-to-gel phase transition behaviors depending on temperature and concentration, have been studied [M. S. Kim, H. Hyun, G. S. Khang et al, Macromolecules, 39, 3099-3102 (2006)].
These studies present biocompatible and biodegradable block copolymers that can be degraded to biological metabolites through dissolution, chemical hydrolysis, etc. and cleared from human body using biodegradable ester-based polymers which are highly soluble in water and organic solvents, nontoxic and immunorejection free and polyethylene glycol which allows control of degradation period of copolymers when introduced through chemical bonding by increasing the amount of water that can be absorbed by the polymers.
Despite these advantages, the conventional temperature-sensitive gels are limited in medical applications because they lack functional groups. In particular, the existing biodegradable polyesters are limited in exhibiting stable drug loading and controlled drug release due to lack functional groups and show side effects such as adsorption to protein surfaces, unwanted modification of drugs, localized accumulation of hydrolysis products, etc.
To introduce functional groups into polyester, copolymerization of cyclic ester compounds with polyethylene glycol, polyvinyl alcohol, heparin, aspartic acid, etc. has been studied [J. Polym. Sci. Part A: Polym Chem. 39 (2001), 2508, J. Appl. Polym. Sci. 81 (2001), 2721]. Although hydrophobicity can be conferred to polyester through approach, further modification is limited because of limitation of the functional groups and the possibility that degradation products may result in undesirable side effects cannot be excluded.